In vivo administration of GM-CSF promotes the clearance of apoptotic cells: effects on monocytes and polymorphonuclear leukocytes.
The clearance of apoptotic cells is crucial to avoid chronic inflammation and autoimmunity. Little is known about the factors that regulate it in vivo. We show that granulocyte-macrophage colony-stimulating factor (GM-CSF) administration to carcinoma patients confers to their leukocytes a significantly higher ability to phagocytose apoptotic cells than before (P < 0.005). GM-CSF increased the concentration of monocytes and polymorphonuclear leukocytes in the peripheral blood and activated circulating polymorphonuclear leukocytes. Both effects abated early after treatment, whereas phagocytosis of apoptotic cells was still significantly higher after 18 days compared with basal values (P < 0.005 and P < 0.025 for monocytes and polymorphonuclear leukocytes, respectively). On in vitro phagocytosis of apoptotic cells monocytes, but not polymorphonuclear leukocytes, up-regulated MHC class II membrane expression. These findings are consistent with the possibility that GM-CSF endows both scavenger and antigen-presenting leukocytes with the ability to internalize apoptotic tumor cells.
Galati
G
G
Second Department of Medicine, University of Milano, Italy.
Rovere
P
P
Citterio
G
G
Bondanza
A
A
Scagliette
U
U
Bucci
E
E
Heltai
S
S
Fascio
U
U
Rugarli
C
C
Manfredi
A A
AA
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000097:blood / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy / Q000473:pathology* / Q000628:therapy; D003110:Colonic Neoplasms / Q000097:blood / Q000473:pathology; D003131:Combined Modality Therapy; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D016898:Interferon-alpha / Q000627:therapeutic use; D019169:Jurkat Cells; D007680:Kidney Neoplasms / Q000097:blood / Q000473:pathology*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000473:pathology; D010587:Phagocytosis / Q000187:drug effects; D014212:Tretinoin / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor