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Defective chemotaxis of human alveolar macrophages
G Poli1, A Erroi, N Polentarutti
1Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Abstract:
Human pulmonary alveolar macrophages (PAM) from normal subjects, unlike peripheral blood monocytes (PBM), are unable to migrate in response to various chemoattractants, such as C5a,f-Met-Leu-Phe (fMLP) and phorbol myristate acetate (PMA). Inflammatory PAM obtained from sarcoid patients also failed to exhibit a chemotactic response. Binding studies using [3H]PDBU demonstrate high affinity receptors for phorbol esters on PAM surface, in a comparable amount (1.5-2.4 X 10(6) receptors/cell) to PBM (8-15 X 10(5) receptors/cell). Moreover, PAM were comparable to PBM in terms of superoxide anion (O2-) release in response to PMA. Therefore, the defective locomotory response of PAM cannot be accounted for by lack of chemoattractant receptors, at least for phorbol esters. Worthy of note, PMA receptors on PAM are able to transduce activating signals for O2- generation. These findings show that competence for chemotaxis is heterogeneously distributed among mononuclear phagocytes.
Insights
Human pulmonary alveolar macrophages (PAM) do not migrate towards chemoattractants, despite having functional receptors. This defective chemotaxis in PAM, unlike peripheral blood monocytes (PBM), indicates varied immune cell responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human pulmonary alveolar macrophages (PAM) and peripheral blood monocytes (PBM) are mononuclear phagocytes with distinct functions.
- PAM from normal subjects and sarcoid patients exhibit defective chemotaxis compared to PBM.
Purpose of the Study:
- To investigate the reasons behind the defective chemotactic response of human pulmonary alveolar macrophages (PAM).
- To compare the expression and function of phorbol ester receptors on PAM and PBM.
Main Methods:
- Chemotaxis assays using chemoattractants like C5a, f-Met-Leu-Phe (fMLP), and phorbol myristate acetate (PMA).
- Binding studies using [3H]PDBU to quantify phorbol ester receptors.
- Superoxide anion (O2-) release assays in response to PMA.
Main Results:
- PAM demonstrated a lack of migration towards C5a, fMLP, and PMA, unlike PBM.
- PAM possess high-affinity phorbol ester receptors comparable in number to PBM.
- PAM effectively released superoxide anions in response to PMA, indicating functional signal transduction.
Conclusions:
- The defective chemotaxis of PAM is not due to a lack of phorbol ester receptors.
- PAM receptors can transduce activating signals for superoxide generation.
- Chemotaxis competence is heterogeneously distributed among mononuclear phagocytes.