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The identity of the retention signal expressed by MARCO^+^ MZMO cells was next determined by investigating the role of specific surface receptors on the MZMO in maintaining the marginal zone structure. The MARCO receptor, in addition to binding to bacteria ([@bib33]), contains an SRCR domain that has been implicated in binding to CD19^+^ lymphocytes ([@bib34], [@bib35]). To determine if MARCO itself is capable of binding to MZBs, we expressed the extracellular domains of MARCO as a soluble molecule ([@bib20]) and used it to stain splenic populations ([Fig. 5](#fig5){ref-type="fig"}) Figure 5.Soluble MARCO receptor (sMARCO) binds preferentially to MZBs. Representative FACS^®^ analysis of spleen cells from WT mice stained with CRI, CD23, and biotinylated sMARCO. Binding of sMARCO to different spleen cell populations was based on gates set on the CRI versus CD23 stain. red, MZBs; blue, follicular B cells; black, non-B cells. The histogram (bottom) shows the mean fluorescence index (MFI) and SD (*n* = 5) for the different populations as well as the avidin (Av) control and block using the MARCO-specific ED31 Ab. Data shown are representative of three independent experiments. . Three populations of cells were distinguished by flow cytometry when stained with CD21 and CD23. Maximal binding to soluble MARCO was observed for the MZBs (CD21^hi^ CD23^low^), whereas the follicular B cells (CD21^low^ CD23^hi^) displayed reduced binding. None of the other splenic populations (T cells, macrophages, or dendritic cells) were capable of binding to soluble MARCO. This binding was specific for the MARCO SRCR domain, as determined by the ability of a monoclonal Ab to this domain (ED31; reference [@bib33]) to block the binding of soluble MARCO to MZBs. When the MARCO-specific Ab was injected i.v. to WT mice it resulted in disruption of the marginal zone structure in which MZBs, identified by CD1d staining, were found in the follicular region whereas MZMOs, identified by ER-TR9 staining, were retained in the marginal zone ([Fig. 6](#fig6){ref-type="fig"}) Figure 6.In vivo disruption of MARCO and MZB interactions leads to MZB migration to the follicle. WT mice were given 100 μg control rat IgG or anti-MARCO (ED31) IgG i.v. 3 h later the mice were killed and the spleens were stained for macrophage and B cell populations. Representative stains of serial sections from at least four different mice are shown. MZMOs were detected with anti-MARCO (blue, top) or ER-TR9 (blue, middle) antibodies whereas metallophilic macrophages were stained with MOMA-1 (brown, bottom). B220^+^ B cells (brown) were stained for positioning of the follicle and MZBs as the CD1^high^ (blue, bottom) population. ×10. Part of the spleen was used for flow cytometric analysis to determine the CD19^+^, CRI^high^, and CD23^low^ populations. Numbers shown are the average of four mice. The percent of CD19^+^ cells for either MZBs or follicular B cells is shown for comparison. Data shown are representative of two independent experiments. . These results suggest that a direct interaction between MZMO and MZBs is mediated by MARCO--MZB binding, through a MARCO ligand expressed on these B cells, and provides a mechanism for the retention of MZBs by MARCO-expressing MZMO cells. Perturbation of this interaction either by disruption of adhesion and/or induction of macrophage activation by MARCO cross-linking results in the appearance of cells expressing a MZB surface phenotype in the follicular zone. |
To address the relevance of the MARCO^+^ MZMO and its retention of MZBs to its contribution to the development of an immune response to pathogens, we injected mice i.v. with rhodamine-conjugated *S. aureus*, which is a known ligand for the MARCO receptor ([@bib12]). Within 30 min of injection bacteria were visualized exclusively bound to the MZMO cells, a role consistent with the phagocytic property of these scavenger receptor--expressing cells ([Fig. 7](#fig7){ref-type="fig"}) Figure 7.*S. aureus* induce MZMO movement and displacement of MZBs. WT mice were injected i.v. with 250 μg heat-killed and rhodamine-conjugated *S. aureus* in PBS. 0.5 or 18 h later the mice were killed and the spleens were sectioned and stained. Representative stains from at least four mice are shown. MARCO^+^ MZMOs (left) are stained blue and B220^+^ B cells are stained brown. The middle shows the same stains as in the left, merged with the fluorescent stain of *S. aureus.* The right shows stains for the CD1^high^ MZB population (blue) and MOMA-1^+^ metallophilic macrophages (brown). ×10. The data shown are representative of two independent experiments. . 18 h after injection the microbes and the MZMO were found to have comigrated into the red pulp and cells with a MZB phenotype (CD1d^high^) were mostly found in the follicular region. These results are consistent with a model in which interaction of *S. aureus* with MARCO on MZMOs results in their migration into the red pulp and the concomitant migration of MZBs into the follicular region as has been reported for LPS and *E. coli* ([@bib8], [@bib9]). The deletion of the inhibitory signaling molecule SHIP results in a similar MZMO migration response, suggesting that MZMO activation can trigger migration into the red pulp. We presume that the likely explanation for the migration seen in response to *S. aureus* ingestion is the activation of MZMOs by their encounter with these bacteria as has been described ([@bib36], [@bib37]). A similar result was observed for *E. coli* suggesting a more general migratory response by MZMO cells to microbial challenge (unpublished data). The migratory response of the MZMO, carrying Ag to the red pulp, could simply be a method of clearance of particulate Ags or alternatively MZMOs could function as Ag transporters/presenters and supporters of plasmablast formation shown to take place in the red pulp ([Fig. 8](#fig8){ref-type="fig"} Figure 8.Proposed model for interactions between MZMO and MZB and the response of these cells to blood-borne pathogens. In the marginal zone (MZ), MZBs interact with the MZMO via the MARCO receptor (a) and with stromal elements via the ICAM/VCAM and their respective ligands LFA-1 and α4β1 (b). Upon phagocytosis of particulate Ags, the MARCO^+^ MZMOs migrate to the red pulp (c) and the majority of the MZBs migrate to the follicle where they interact with cells such as dendritic and follicular dendritic (d, DC and FDC). In the early response to T cell--independent Ags, the MZB also has the capacity to migrate to the red pulp to take part in plasma cell formation (e), where a possible interaction with MZMOs and MZBs may take place. ; references [@bib38]--[@bib40]). This has previously been reported to be a function of dendritic cells in the T/B cell border of the follicle and by macrophages supporting B1 B cells in the peritoneum ([@bib10]). Interestingly, Kang et al. ([@bib14]) recently showed that phagosomes in MZMOs, after uptake of dextran polysaccarides via SIGN-RI did not stain positive for the endosomal markers LAMP-1 and transferrin. This suggests that Ags taken up by MZMOs may not necessarily take the route of normal phagosome maturation ([@bib41]) resulting in destruction or Ag presentation and thus could provide a mechanism to transport intact Ag to the red pulp by MZMOs. |
These results suggest that the interaction of MZMO cells with MZBs is required to maintain the marginal zone structure and that this association is perturbed upon MZMO binding and activation by microbial pathogens. It is likely that the MZBs migrate into the follicular zone in response to CXCL13 ([@bib9]) in the absence of retention signals from the MARCO^+^ MZMO. This pathway is likely to be independent of the integrin pathway involving stromal VCAM/ICAM and B cell LFA-1/α4β1 because disruption of that pathway with antibodies to LFA-1 and α4β1 results in the release of MZBs to the blood stream ([@bib9]), not their migration into the follicle, in contrast to the results presented here ([Fig. 8](#fig8){ref-type="fig"}). In addition, we see no effect on the localization of MZMO cells using antibodies to the stromal integrins, nor do we observe effects on their ligand expression when MZMO cells are triggered to migrate (unpublished data). These pathways are thus likely to serve different functions in the organization of the marginal zone, with the MZMO pathway specific for the antimicrobial response, leading to internalization of the organism and trafficking of B cells into the follicular zone to propagate the immune responses. MZBs have the capacity to bind polysaccharide Ags through complement-mediated pathways and transport these to the follicular area of the spleen ([@bib6], [@bib8], [@bib42]). The events we have described appear to be another mechanism for delivery of MZBs and Ag to the T cell--rich follicular region. MZBs have mostly been implicated in the response to T cell--independent Ags, however, they are also capable of presenting Ags ([@bib43]) and may thus be important both for the T cell--dependent and --independent phase of the earliest defense against a pathogen. |
We would like to thank members of the Ravetch and Steinman labs at The Rockefeller University, especially Pierre Bruhns, Patrick Smith, Maggi Pack, Chae Gyu Park, and Sayori Yamazaki for technical assistance and comments on the manuscript. We also thank Dr. Jeffrey Pollard for op/op mice and Dr. Timo Pikkarainen for reagents and helpful comments. |
This work was supported by the Swedish Cancer Society and the NIH. |
*Abbreviations used in this paper:* Btk, Bruton\'s tyrosine kinase; ES, embryonic stem; MZB, marginal zone B cell; MZMO, marginal zone macrophage; SHIP, SH2-containing inositol-5-phosphatase 1. |
Q: |
How can I Check the current value which is already passed or not in an array in nested foreach in php |
My array |
$key1=> |
Array |
( |
[0] => 1 |
[1] => 2 |
[2] => 7 |
[3] => 11 |
[4] => 12 |
[5] => 17 |
[6] => 18 |
) |
$_POST['name']=> |
Array |
( |
[0] => General |
[1] => General |
[2] => Outdoors |
[3] => Dining |
[4] => Kitchen |
) |
Here is my code, |
foreach ($key1 as $key => $value) { |
// echo $value; |
foreach ($_POST['name'] as $key => $value1) { |
//echo $value; |
$subQueryCond .=' AND '.$value1.' LIKE ' .$value ; |
} |
} |
While my Ajax calls this nested loop occurs.. |
Inside this I wrote a query.. |
If one value is passed. |
The query is in the format of AND 'General' LIKE 1. |
And if another value is passed in the $key1 it pass the query two times. |
It's like How many arrays are given that much time that query was passed.. |
So,here I would like to restrict the $value if it already came.. |
if two values were given,it pass the query in the following manner |
AND General LIKE 1 |
AND Outdoors LIKE 1 |
AND General LIKE 7 |
AND Outdoors LIKE 7 |
And my desired query must be in the form of |
AND General LIKE 1 |
AND General LIKE 7 |
AND Outdoors LIKE 7 |
can someone help me.. |
A: |
This will work for you... |
<?php |
$subQueryCond= ''; |
foreach ($key1 as $key => $value) |
{ |
foreach ($_POST['name'] as $key => $value1) |
{ |
$subQueryCond['AND '.$value1.' LIKE ' .$value] = ' AND '.$value1.' LIKE ' .$value ; |
} |
} |
echo "<pre>"; print_r($subQueryCond); |
$query = implode('',$subQueryCond) ; |
print_r($query); |
?> |
just make an array with unique keys to value, then use implode() function to make query string... |
Safety of union home care aides in Washington State. |
A rate-based understanding of home care aides' adverse occupational outcomes related to their work location and care tasks is lacking. Within a 30-month, dynamic cohort of 43 394 home care aides in Washington State, injury rates were calculated by aides' demographic and work characteristics. Injury narratives and focus groups provided contextual detail. Injury rates were higher for home care aides categorized as female, white, 50 to <65 years old, less experienced, with a primary language of English, and working through an agency (versus individual providers). In addition to direct occupational hazards, variability in workload, income, and supervisory/social support is of concern. Policies should address the roles and training of home care aides, consumers, and managers/supervisors. Home care aides' improved access to often-existing resources to identify, manage, and eliminate occupational hazards is called for to prevent injuries and address concerns related to the vulnerability of this needed workforce. |
{-# LANGUAGE FlexibleContexts #-} |