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Department, Institute
Keywords
- CD146 (1)
- Confocal microscopy (1)
- Endothelial cells (1)
- Matrix metalloproteases (1)
- Proteasome maturation (1)
- Tetramerisation (1)
- Vascular permeability (1)
- shedding (1)
Neutrophils and lymphocytes are recruited to sites of inflammation and require the adhesion molecule L-selectin (CD62L) for adherence to endothelial cells. Nucleotides released from activated or dying cells at sites of inflammation can mediate signaling through purinergic receptor family II, resulting in CD62L shedding. Activation of B lymphocytes requires the complement receptor type II (CD21) and at the same time leads to shedding of CD21. Both CD62L and CD21 shedding possibly depends on the same families of proteases. In the present study, we characterized peripheral blood naive and memory cells and neutrophils for CD62L surface expression and analyzed benzoyl-benzoyl triphosphate (BzATP)-induced shedding. BzATP is able to induce CD62L shedding in naive and memory lymphocytes, but not in neutrophils. CD21 shedding can be induced through activation of the B cell receptor (BCR) or with mitogens. Here we show that CD21 is also susceptible to BzATP-induced shedding on peripheral B cells. In addition, using receptor inhibitors, we show that shedding of CD21 and CD62L is mediated via the P2X7R. P2X7R-mediated CD62L and CD21 shedding could occur as a result of extracellular accumulated ATP and may have an influence on leukocyte migrational behavior and BCR-mediated signaling.
Background: Migration of mature and immature leukocytes in response to chemokines is not only essential during inflammation and host defense, but also during development of the hematopoietic system. Many molecules implicated in migratory polarity show uniform cellular distribution under non-activated conditions, but acquire a polarized localization upon exposure to migratory cues.
Methodology/Principal Findings: Here, we present evidence that raft-associated endocytic proteins (flotillins) are preassembled in lymphoid, myeloid and primitive hematopoietic cells and accumulate in the uropod during migration. Furthermore, flotillins display a polarized distribution during immunological synapse formation. Employing the membrane lipid-order sensitive probe Laurdan, we show that flotillin accumulation in the immunological synapse is concomittant with membrane ordering in these regions.
Conclusions: Together with the observation that flotillin polarization does not occur in other polarized cell types such as polarized epithelial cells, our results suggest a specific role for flotillins in hematopoietic cell polarization. Based on our results, we propose that in hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization.
