rTNF alpha facilitates human polymorphonuclear leukocyte adherence to fibrinogen matrices with mobilization of specific and tertiary but not azurophilic granule markers.
rTNF alpha facilitates highly reproducible adherence of polymorphonuclear leukocyte (PMN) to fibrinogen-coated surfaces in a concentration- and time-dependent manner. The adhesion was maximal with 1.0 nM rTNF alpha within 40-50 min at 37 degrees C. A monoclonal antibody (1B4) directed toward the beta 2-chain of the integrin receptor for fibrinogen (CD11b, CD18) completely inhibited the rTNF alpha induced adhesion. TNF alpha caused a time-dependent secretion of the granule markers gelatinase and lactoferrin but no liberation of myeloperoxidase and minimal production of A alpha(1-21), a specific cleavage product of fibrinogen generated by elastase, as markers for the azurophilic granule. PMN adhered to fibrinogen in the presence of rTNF alpha could be further stimulated with cytochalasin B and N-formyl-methionyl-leucyl-phenylalanine (FMLP) to release azurophilic granule markers as measured by increasing MPO activity and A alpha(1-21) production over time. Thus the rTNF alpha-facilitated adherence of PMN to a fibrinogen matrix provides a system for partial activation of PMN resulting in release of markers of specific and tertiary but not azurophilic granules. Moreover, these conditions should provide an opportunity to define more clearly the signal transduction processes involved in azurophilic granule release.
Hanlon
W A
WA
Department of Immunology and Inflammation, MSDRL, Rahway, New Jersey 07065.
Stolk
J
J
Davies
P
P
Humes
J L
JL
Mumford
R
R
Bonney
R J
RJ
D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism*; D018093:Gelatinases; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010434:Pepsin A / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen; D009195:Peroxidase; D007781:Lactoferrin; D010434:Pepsin A; D018093:Gelatinases