Increased macrophage inflammatory protein-1alpha and macrophage inflammatory protein-1beta levels in bronchoalveolar lavage fluid of patients affected by different stages of pulmonary sarcoidosis.
Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta are two CC chemokines that induce lymphocyte migration. MIP-1alpha preferentially mediates chemotaxis of CD8 rather than CD4 lymphocytes, whereas the reverse is true for MIP-1beta. Both these chemokines recognize CCR5 as a cellular receptor in T lymphocytes and alveolar macrophages. We measured the concentrations of MIP-1alpha and MIP-1beta in bronchoalveolar lavage fluid (BALF) of 30 subjects affected by different stages of pulmonary sarcoidosis and 18 healthy normal subjects. We also evaluated the expression of CCR5 in alveolar macrophages and lymphocytes. The BALF concentrations of MIP-1alpha were significantly increased only in Stage II and III sarcoidosis. On the contrary, the concentrations of MIP-1beta were significantly increased at all stages. A striking increase of CCR5 expression was observed in both lymphocytes and macrophages of all patients, along with a trend to decreased positivity from Stage I to III of the disease. The MIP-1beta concentrations correlated with the number of total (r = 0.65, p = 0.0001) and both CD4 (r = 0.64, p = 0.0001) and CD8 (r = 0.62, p = 0.0001) lymphocytes; on the contrary, the MIP-1alpha concentrations correlated only with CD8 lymphocytes (r = 0.45, p = 0.002). Finally, significant negative correlations were observed between the neutrophil percentage and CCR5 expression in alveolar macrophages (r = -0.53, p = 0.005) and lymphocytes (r = -0.43, p = 0.01). Our results help to explain the mechanism of CD4 and CD8 recruitment and the possible involvement of CC chemokines in the fibrotic progression of sarcoidosis.
Capelli
Armando
A
"Salvatore Maugeri" Foundation, Istituto de Ricovero e Cura a Carattere Scientifico (IRCCS), Scientific Institute of Veruno (Italy), Division of Pulmonary Disease, Veruno, Italy. acapelli@fsm.it
Di Stefano
Antonino
A
Lusuardi
Mirco
M
Gnemmi
Isabelle
I
Donner
Claudio F
CF
D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D015704:CD4 Antigens / Q000032:analysis; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000032:analysis; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000032:analysis*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000032:analysis; D012129:Respiratory Function Tests; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism*
D015704:CD4 Antigens; D016827:CD8 Antigens; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5