PMID- 12598424 OWN - NLM STAT- MEDLINE DCOM- 20030827 LR - 20181113 IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 138 IP - 4 DP - 2003 Feb TI - CC chemokines induce P-selectin-dependent neutrophil rolling and recruitment in vivo: intermediary role of mast cells. PG - 698-706 AB - 1. Based on in vitro chemotaxis experiments, it is widely held that CC chemokines, such as macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage chemotactic protein-1 (MCP-1) mainly support lymphocyte trafficking. 2. The objective of the present study was to examine the role of MIP-1alpha and MCP-1 in neutrophil recruitment in vivo by use of intravital microscopy of the mouse cremaster microcirculation. 3. MIP-1alpha and MCP-1 caused a dose-dependent increase in leukocyte rolling, adhesion and recruitment. Indeed, neutrophils comprised more than 85% of the leukocyte response to MIP-1alpha and MCP-1. An anti-P-selectin antibody reduced MIP-1alpha and MCP-1-provoked leukocyte rolling by more than 94%. Concomitantly, firm adhesion and extravasation of neutrophils in response to MIP-1alpha and MCP-1 challenge were significantly decreased by more than 78 and 84%, respectively. In contrast, an anti-E-selectin antibody had no influence on CC chemokine-induced neutrophil recruitment. 4. Flow cytometric analysis revealed that MIP-1alpha and MCP-1 had no effect on P-selectin expression on endothelial cells, suggesting that neutrophil recruitment elicited by CC chemokines in vivo is not mediated via a direct effect on the endothelium but rather via an indirect effect involving activation of an intermediary tissue cell. Indeed, it was found that MIP-1alpha-induced neutrophil accumulation was significantly decreased by 58% in mast cell-deficient mice. 5. These findings demonstrate that CC chemokines trigger P-selectin-dependent rolling and tissue recruitment of neutrophils via tissue mast cells in vivo and suggest that CC chemokines may also be important targets in neutrophil-mediated tissue damage in multicellular organs. FAU - Wan, Ming Xiu AU - Wan MX AD - Department of Surgery, Malmo University Hospital, Lund University, 20502 Malmo, Sweden. FAU - Wang, Yusheng AU - Wang Y FAU - Liu, Qing AU - Liu Q FAU - Schramm, Rene AU - Schramm R FAU - Thorlacius, Henrik AU - Thorlacius H LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Chemokines, CC) RN - 0 (P-Selectin) SB - IM MH - Animals MH - Chemokines, CC/*pharmacology MH - Dose-Response Relationship, Drug MH - Male MH - Mast Cells/*drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Neutrophil Infiltration/*drug effects/physiology MH - Neutrophils/drug effects/metabolism MH - P-Selectin/*metabolism PMC - PMC1573702 EDAT- 2003/02/25 04:00 MHDA- 2003/08/28 05:00 PMCR- 2004/02/01 CRDT- 2003/02/25 04:00 PHST- 2003/02/25 04:00 [pubmed] PHST- 2003/08/28 05:00 [medline] PHST- 2003/02/25 04:00 [entrez] PHST- 2004/02/01 00:00 [pmc-release] AID - 0705094 [pii] AID - 10.1038/sj.bjp.0705094 [doi] PST - ppublish SO - Br J Pharmacol. 2003 Feb;138(4):698-706. doi: 10.1038/sj.bjp.0705094.