The CXC chemokine NAP-2 mediates differential heterologous desensitization of neutrophil effector functions elicited by platelet-activating factor.
During early inflammation, the chemoattractants neutrophil-activating peptide-2 (NAP-2), platelet-activating factor (PAF), and complement component C5a are rapidly generated within the vasculature and potently induce effector functions in neutrophils, such as chemotaxis and degranulation. We investigated whether these mediators would cross-desensitize each other's activities on isolated neutrophils. We demonstrate that NAP-2 and C5a desensitize degranulation of neutrophils in response to PAF. However, whereas C5a-mediated desensitization correlated with the downregulation of PAF binding sites on neutrophils, NAP-2 did not regulate PAF receptors, nor did it modulate their calcium signaling. In further contrast to C5a, which desensitized PAF-induced neutrophil chemotaxis, NAP-2 did not affect the chemotatic response to PAF. These observations indicate that NAP-2 mediates selective desensitization of PAF-induced neutrophil degranulation by a mechanism downstream from PAF receptors, still allowing migration toward PAF. Thus, a role for NAP-2 may be to limit PAF-dependent vascular tissue damage by preventing degranulation of neutrophils without affecting their migration into the inflamed tissue.
Schwartzkopff
Franziska
F
Department of Immunology and Cell Biology, Research Center Borstel, D-23845 Borstel, Germany.
Brandt
Ernst
E
Petersen
Frank
F
Flad
Hans-Dieter
HD
Bock
Lothar
L
Ludwig
Andreas
A
D001779:Blood Coagulation Factors / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D015550:Cell Degranulation / Q000502:physiology; D002469:Cell Separation; D019743:Chemokines, CXC / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology; D015936:Complement C5a / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D006801:Humans; D018375:Neutrophil Activation / Q000502:physiology*; D009504:Neutrophils / Q000378:metabolism; D010455:Peptides / Q000502:physiology*; D010972:Platelet Activating Factor / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D001620:beta-Thromboglobulin
D001779:Blood Coagulation Factors; D019743:Chemokines, CXC; C061615:PPBP protein, human; D010455:Peptides; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D001620:beta-Thromboglobulin; C039351:platelet activating factor receptor; C018329:low affinity platelet factor 4; D015936:Complement C5a