Downmodulation of CXCL8/IL-8 receptors on neutrophils after recruitment in the airways.
BACKGROUND
CXCL8/IL-8 is the most significant chemokine for neutrophils, and CXC chemokine receptor (CXCR) 1 and 2 are its 2 receptors, which are downmodulated by CXCL8/IL-8 and endotoxin on activated neutrophils.


OBJECTIVE
We sought to evaluate the expression of the CXCL8/IL-8 receptors and the activation marker CD11b on neutrophils in peripheral blood and in the site of airway inflammation.


METHODS
The flow cytometric expression of CXCR1, CXCR2, and CD11b was evaluated on peripheral blood and induced sputum neutrophils in patients with nonsevere asthma with greater than 60% sputum neutrophils, in patients with chronic obstructive pulmonary disease (COPD), and in healthy control subjects.


RESULTS
Asthmatic patients and patients with COPD had comparable expressions of CXCR1, CXCR2, and CD11b on peripheral blood and sputum neutrophils. Compared with control subjects, the peripheral neutrophil expression of CXCR2 was lower in patients with COPD ( P = .03) and that of CD11b was higher in asthmatic patients and patients with COPD ( P < .02 and P < .002). The expression of the CXCL8/IL-8 receptors on sputum neutrophils was markedly lower than on peripheral blood neutrophils ( P < .0001). The downmodulation of CXCL8/IL-8 receptors was also present in healthy control subjects but less than that seen in asthmatic patients. The difference between peripheral blood and sputum expression of CXCL8/IL-8 receptors correlated with serum CXCL8/IL-8 levels. In asthmatic patients the expression of CXCR1 and CXCR2 on sputum neutrophils negatively correlated with sputum neutrophils.


CONCLUSIONS
In neutrophilic asthma the expression of CXCL8/IL-8 receptors on peripheral and sputum neutrophils is similar to COPD and negatively correlated with the inflammatory infiltrate in the airways. The downmodulation of CXCL8/IL-8 receptors detected in the airways should be taken into account for an eventual therapeutic inhibition of these receptors.
Pignatti
Patrizia
P
Servizio Autonomo di Allergologia e Immunologia Clinica, Fondazione Salvatore Maugeri, IRCCS, Pavia, Italy. ppignatti@fsm.it
Moscato
Gianna
G
Casarini
Simona
S
Delmastro
Monica
M
Poppa
Mariangela
M
Brunetti
Giuseppe
G
Pisati
Paolo
P
Balbi
Bruno
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000276:immunology*; D018845:CD11 Antigens / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D023062:Receptors, Interleukin-8A / Q000032:analysis* / Q000096:biosynthesis; D023063:Receptors, Interleukin-8B / Q000032:analysis* / Q000096:biosynthesis; D013183:Sputum / Q000166:cytology / Q000276:immunology
D018845:CD11 Antigens; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B