Alveolar macrophages lack CCR2 expression and do not migrate to CCL2

AbstractBackgroundThe recruitment of mononuclear cells has important implications for tissue inflammation. Previous studies demonstrated enhanced CCR1 and CCR5 expression and decreased CCR2 expression duringin vitromonocyte to macrophage differentiation. To date, no study examined thein vivodifferences in chemokine receptor expression between human peripheral blood monocytes and alveolar macrophages.MethodsWe examined the expression of these receptors in human peripheral blood monocytes and alveolar macrophages using microarray analysis, reverse-transcriptase PCR, flow cytometry and migration analyses.ResultsIn contrast to peripheral blood monocytes, alveolar macrophages did not express the CCL2 receptor, CCR2, and did not migrate toward CCL2. In contrast, monocytes and freshly isolated resident alveolar macrophages both migrated towards CCL3. However, up to 6-fold more monocytes migrated toward equivalent concentrations of CCL3 than did alveolar macrophages from the same donor. While peripheral blood monocytes expressed the CCL3 receptor, CCR1, alveolar macrophages expressed the alternate CCL3 receptor, CCR5. The addition of anti-CCR5 blocking antibodies completely abrogated CCL3-induced migration in alveolar macrophages, but did not affect the migration of peripheral blood monocytes.ConclusionThese data support the specificity of CCL2 to selectively drive monocyte, but not alveolar macrophage recruitment to the lung and CCR5 as the primary macrophage receptor for CCL3.