PMID- 1469085 OWN - NLM STAT- MEDLINE DCOM- 19930127 LR - 20181113 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 90 IP - 6 DP - 1992 Dec TI - Entactin stimulates neutrophil adhesion and chemotaxis through interactions between its Arg-Gly-Asp (RGD) domain and the leukocyte response integrin. PG - 2251-7 AB - Entactin is an integral component of basement membranes that plays a major role in basement membrane assembly through its ability to bind avidly to both laminin and type IV collagen. Because neutrophil (PMN) interactions with entactin have not been examined, we investigated the ability of natural and recombinant entactin to mediate PMN adhesion and chemotaxis. With both forms of entactin, we observed that entactin-coated surfaces promoted PMN adhesion and that entactin stimulated PMN chemotaxis. The increase in adhesion to entactin over control was two to threefold whereas the chemotactic response to 15 ng/ml (1 x 10(-10) M) entactin was equivalent to the chemotactic response elicited with 1 x 10(-8) M formyl-methionyl-leucyl-phenylalanine (fMLP). HL-60 cells, after differentiation with dimethylsulfoxide, also demonstrated adhesion and chemotaxis to entactin. A synthetic peptide of the Arg-Gly-Asp (RGD) domain in entactin, SIGFRGDGQTC (S-RGD), mediated PMN adhesion and chemotaxis, and preexposure of PMN to S-RGD blocked PMN adhesion and chemotaxis induced by entactin without diminishing the adhesive and chemotactic activities of fMLP. In contrast, preexposure to peptides SIGFRGEGQTCA or SIGFKGDGQTCA had no effect. The findings with synthetic peptides were confirmed with a recombinant entactin mutant in which aspartic acid at residue 674 was replaced with glutamic acid, thus converting the RGD sequence of entactin to RGE. RGE-entactin was neither adhesive nor chemotactic for neutrophils. Monoclonal antibodies to the leukocyte response integrin (LRI) and the integrin-associated protein blocked entactin-mediated adhesion and chemotaxis whereas monoclonal antibodies to beta 1 and beta 2 integrins had no effect and PMN from an individual with leukocyte-adhesion deficiency adhered normally to entactin-coated surfaces. These data demonstrate that entactin mediates biologically and pathologically important functions of PMN through its RGD domain and that LRI, which has been shown previously to mediate RGD-stimulated phagocytosis, is also capable of mediating RGD-stimulated PMN adhesion and chemotaxis. FAU - Senior, R M AU - Senior RM AD - Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110. FAU - Gresham, H D AU - Gresham HD FAU - Griffin, G L AU - Griffin GL FAU - Brown, E J AU - Brown EJ FAU - Chung, A E AU - Chung AE LA - eng GR - AI 23790/AI/NIAID NIH HHS/United States GR - GM 38330/GM/NIGMS NIH HHS/United States GR - HL 29594/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Integrins) RN - 0 (Membrane Glycoproteins) RN - 0 (Membrane Proteins) RN - 0 (Oligopeptides) RN - 0 (nidogen) RN - 78VO7F77PN (arginyl-glycyl-aspartic acid) RN - 9001-32-5 (Fibrinogen) SB - IM MH - Amino Acid Sequence MH - Cell Adhesion/*drug effects MH - Chemotaxis, Leukocyte/*drug effects MH - Fibrinogen/physiology MH - Humans MH - Immunologic Techniques MH - In Vitro Techniques MH - Integrins/*physiology MH - Membrane Glycoproteins/*pharmacology MH - Membrane Proteins/metabolism MH - Molecular Sequence Data MH - Neutrophils/*physiology MH - Oligopeptides MH - Structure-Activity Relationship MH - Tumor Cells, Cultured PMC - PMC443376 EDAT- 1992/12/01 00:00 MHDA- 1992/12/01 00:01 PMCR- 1992/12/01 CRDT- 1992/12/01 00:00 PHST- 1992/12/01 00:00 [pubmed] PHST- 1992/12/01 00:01 [medline] PHST- 1992/12/01 00:00 [entrez] PHST- 1992/12/01 00:00 [pmc-release] AID - 10.1172/JCI116111 [doi] PST - ppublish SO - J Clin Invest. 1992 Dec;90(6):2251-7. doi: 10.1172/JCI116111.