Defective chemotaxis of human alveolar macrophages.
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.
Poli
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Erroi
A
A
Polentarutti
N
N
Vago
L
L
Luisetti
M
M
Biondi
A
A
Mantovani
A
A
D000954:Antigens, Surface / Q000032:analysis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004112:Dimercaprol; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology; D012507:Sarcoidosis / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000954:Antigens, Surface; D004112:Dimercaprol; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate