Increased Macrophage Inflammatory Protein-1 α and Macrophage Inflammatory Protein-1 β Levels in Bronchoalveolar Lavage Fluid of Patients Affected by Different Stages of Pulmonary Sarcoidosis

Abstract

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.

Alveolar macrophages are the main source for tumour necrosis factor‐α in patients with sarcoidosis

“…Recent data indicate that only a subpopulation of alveolar macrophages is responsible for the secretion of TNF-a in patients with pulmonary sarcoidosis [24]. Notably, in the present study, Alveolar macrophages of patients with sarcoidosis exhibit multiple secretory cell functions in that they release other cytokines such as IL-15, growth factors, and chemokines such as monocyte chemotactic protein-1, RANTES (regulated, on activation, T-cell expressed and secreted) and macrophage inflammatory proteins-1a and -1b [2,26,27]. Thus, alveolar macrophages may strongly affect T-cell recruitment and T-cell response [28].…”

Relationship between radiologic patterns, pulmonary function values and bronchoalveolar lavage fluid cells in newly diagnosed sarcoidosis

“…It is thought that the increased BALF neutrophil and/or eosinophil count is associated with a more advanced, chronic disease course (17,(31)(32)(33). The increase of the macrophages and neutrophil count, decrease of lymphocyte count and CD4/CD8 ratio with increased radiographic stage of sarcoidosis in BALF in patient with newly diagnosed sarcoidosis have been documented (17,23). In line with these observations, we found significant differences (P=0.021) between the percentage of neutrophils of BALF in radiographic stages I and III in our sample.…”

“…Recently, the correlation between disease severity in CT, functional impairment and radiographic stages of sarcoidosis, as well as pulmonary function tests (PFT) and bronchoalveolar lavage fluid (BALF) cells, have been discussed in the literature (5,(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). However, few systematic evaluations exist exploring the relationships between the various HRCT findings (e.g., micronodules, macronodules, irregular linear opacities, interlobular septal thickening, fibrotic changes, etc.…”

Genetics of Sarcoidosis

“…[45] These chemokines play an important role in lymphocyte and monocyte recruitment and activation in sarcoidosis. [46,47] In Sarcoidosis, CCR5 expression is up-regulated in Bronchoalveolar lavage (BAL) macrophages and lymphocytes [48,49] and levels of the CCR5 ligands, CCL3 and CCL5, correlate with risk of disease progression. [50][51][52] The CCR5Δ32 null allele results a 32bp deletion in the CCR5 gene and produces a non-functional receptor that is unable to bind to its ligand [53].…”