Interleukin-8 induces changes in human neutrophil actin conformation and distribution: relationship to inhibition of adhesion to cytokine-activated endothelium.
Interleukin-8 (IL-8) induces diverse biological responses in neutrophils, including inhibition of adhesion to cytokine-activated endothelium, which we have termed the leukocyte adhesion inhibition (LAI) effect. Pretreatment of neutrophils with cytochalasin B abolished the LAI effect of IL-8, suggesting a microfilament-dependent mechanism. Interleukin-8 induced a rapid increase (less than or equal to 15 s) in the polymerization of actin filaments in human neutrophils that was blocked by pretreatment with cytochalasin B. F-actin depolymerization occurred gradually at a rate inversely proportional to IL-8 concentration. This temporal pattern of actin polymerization-depolymerization was similar to that induced by other chemotactic factors such as C5a and N-formylmethionyl-leucyl-phenylalanine, which also exhibit a marked LAI effect, but the lipid mediators, leukotriene B4 and platelet-activating factor, lack any significant LAI effect. Scanning confocal microscopy demonstrated that neutrophil actin microfilaments undergo a dramatic rearrangement prior to detachment of the neutrophil from a surface. We suggest that the ability of IL-8 and certain other leukocyte agonists to regulate the actin polymer network of neutrophils may play an important role in adhesive interactions with the vascular endothelium.
Westlin
W F
WF
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115.
Kiely
J M
JM
Gimbrone
M A
MA
D000199:Actins / Q000737:chemistry*; D002630:Chemotactic Factors / Q000494:pharmacology; D015936:Complement C5a / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D007957:Leukocyte Adherence Inhibition Test; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000737:chemistry* / Q000166:cytology; D011108:Polymers; D011487:Protein Conformation / Q000187:drug effects
D000199:Actins; D002630:Chemotactic Factors; D016209:Interleukin-8; D011108:Polymers; D003571:Cytochalasin B; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a