CD45 modulation of CXCR1 and CXCR2 in human polymorphonuclear leukocytes.

Abstract:

:All leukocytes express the cell surface glycoprotein CD45, which has intrinsic intracellular protein tyrosine phosphatase activity. CD45 is known to play a regulatory role in activation-induced signaling in lymphocytes; however, little is known of its role in non-lymphoid leukocytes. Therefore, we examined the potential effect of CD45 on chemokine-induced signaling in human neutrophils (polymorphonuclear cells, PMN). Treating isolated PMN for 2 h with an anti-CD45RB antibody (Bra11) down-modulated expression of the chemokine receptors CXCR1 and CXCR2 to 44 +/- 10% and 47 +/- 9% of their respective controls. The tyrosine kinase inhibitors genistein and herbimycin A significantly inhibited the Bra11-induced down-modulation of CXCR1 and CXCR2. Furthermore, Bra11-treated PMN were functionally inhibited in their capacity to exhibit IL-8-induced transient intracellular Ca2+ increases. Selected targeting of CXC receptors is indicated by the fact that N-formyl-Met-Leu-Phe (fMLP) receptor expression and function were not lost following Bra11 treatment. The effect of Bra11 on IL-8-mediated function and receptor expression was paralleled by decreased tyrosine phosphorylation of a 54- to 60-kDa protein. These findings indicate that CD45 can act to modulate PMN responses to chemokines; thus agents regulating CD45 can potentially modulate leukocyte traffic and may represent a novel therapeutic approach towards the treatment of inflammatory diseases.

journal_name

Eur J Immunol

authors

Mitchell GB,Khandaker MH,Rahimpour R,Xu L,Lazarovits AI,Pickering JG,Suria H,Madrenas J,Pomerantz DK,Feldman RD,Kelvin DJ

doi

10.1002/(SICI)1521-4141(199905)29:05<1467::AID-IMM

keywords:

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

1467-76

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

29

pub_type

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