Differential effects of neutrophil-activating peptide 1/IL-8 and its homologues on leukocyte adhesion and phagocytosis.
Several structural homologues of the chemotactic peptide neutrophil-activating peptide 1/IL-8 (NAP-1/IL-8) were tested for their ability to influence the expression and function of adhesion-promoting receptors on human polymorphonuclear leukocytes (PMN). NAP-2, melanoma growth stimulatory activity, and two forms of NAP-1/IL-8 (ser-NAP-1/IL-8 and ala-NAP-1/IL-8, consisting of 72 and 77 amino acids, respectively), each caused an increase in the expression of CD11b/CD18 (CR3) and CR1, which was accompanied by a decrease in the expression of leukocyte adhesion molecule-1 (LAM-1, LECAM-1). The binding activity of CD11b/CD18 was also enhanced 3- to 10-fold by these peptides, but enhanced function was transient: binding of erythrocytes coated with C3bi reached a maximum by 30 min and declined thereafter. Ser-NAP-1/IL-8, ala-NAP-1/IL-8, NAP-2, and melanoma growth stimulatory activity also caused a two- to threefold enhancement of the phagocytosis of IgG-coated erythrocytes (EIgG) by PMN without causing a large increase in the expression of Fc gamma receptors. Enhanced phagocytosis of EIgG appeared to be mediated through CD11b/CD18, because F(ab')2 fragments of an antibody directed against CD18 inhibited NAP-1/IL-8-stimulated ingestion of EIgG. The four active peptides caused a rapid, transient increase in the amount of F-actin within PMN, indicating that they are capable of influencing the structure of the microfilamentous cytoskeleton, which participates in phagocytosis. Two other NAP-1/IL-8-related peptides, platelet factor 4 and connective tissue-activating peptide III, were without effect on expression of CD11b/CD18, CR1, and LAM-1, binding activity of CD11b/CD18, or Fc-mediated phagocytosis, and increased actin polymerization only slightly. Our observations indicate that several members of the NAP-1/IL-8 family of peptides were capable of promoting integrin-mediated adhesion and Fc-mediated phagocytosis, processes important in the recruitment of PMN to sites of inflammation and antimicrobial responses of PMN.
Detmers
P A
PA
Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021.
Powell
D E
DE
Walz
A
A
Clark-Lewis
I
I
Baggiolini
M
M
Cohn
Z A
ZA
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology; D000943:Antigens, Differentiation / Q000032:analysis; D018821:CD18 Antigens; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis; D003179:Complement C3b / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000494:pharmacology*; D019041:L-Selectin; D016177:Macrophage-1 Antigen / Q000032:analysis / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D011951:Receptors, Complement / Q000032:analysis; D017463:Receptors, Complement 3b; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D012756:Sheep
D000199:Actins; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D011961:Receptors, Fc; D017452:Receptors, IgG; D019041:L-Selectin; D003179:Complement C3b