The Dissociation by Colchicine of Phagocytosis from Increased Oxygen Consumption in Human Leukocytes*

Malawista, Stephen E.; Bodel, Phyllis

doi:10.1172/jci105579

Cited by 160 publications

(73 citation statements)

References 33 publications

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“…These drugs also appear to inhibit extracellular release of cathepsin and acid (a-naphthyl) phosphatase, although this could not be measured di- rectly. These results are consistent with the effects of these drugs in other experimental systems, i.e., the "stabilization" of isolated lysosomes by cortisol ( 3 , 4 ) and the inhibition of degranulation within intact, phagocytizing human leukocytes, by colchicine (8).…”

Section: Discussionsupporting

confidence: 88%

Mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis: inhibition by colchicine and cortisol but not by salicylate

Wright

Malawista

1973

Arthritis & Rheumatism

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Granular (lysosomal) enzymes are released from phagocytizing human leukocytes and are believed to be important in the tissue damage of acute inflammation. Antiinflammatory drugs such as colchicine, cortisol, and salicylate have been reported to "stabilize" isolated lysosomes or to inhibit degranulation within cells. These drugs, by altering mobilization of granular enzymes within cells, might be expected to affect the release of these enzymes outside of cells. Human blood leukocytes, isolated by dextran sedimentation, were incubated in autologous serum-buffer media, with or without colchicine (2.5 x 10-SM), cortisol (5 x 104M), Na salicylate (2.2 x 10JM), or acetylsalicylic acid (lo-"), for 30 minutes, 37.9 C, and then with or without heat-killed staphylococci. Both cellular and extracellular activities of granular enzymes (lysozyme, acid phosphatase, cathepsin) were measured. Both intracellular mobilization and extracelluiar release of granular enzymes by phagocytizing leukocytes are inhibited by colchicine and cortisol. Salicylate, contrary to suggestions based on studies with isolated lysosomes from liver, did not show these effects. These results may account in part for antiinflammatory effects of colchicine and cortisol, but not of salicylate.Antiiifiammatory drugs are crucial to the management of patients with rheumatic diseases, yet their precise mechanisms of action remain unclear. It is likely that these drugs alter

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Section: Discussionsupporting

confidence: 88%

Mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis: inhibition by colchicine and cortisol but not by salicylate

Wright

Malawista

1973

Arthritis & Rheumatism

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“…Microtubular disruption inhibits secretion of salivary gland mucin (3), of hepatic very low density lipoproteins (4,5), and of albumin and other plasm proteins (6). Microtubule-associated functions may also regulate lysosomal degranulation during phagocytosis (7,8) and influence the conversion of prohormones into their active forms (9). The colchicine-induced inhibition of the mobility of membrane components (10) and changes in plasma membrane microviscosity associated with phagocytosis (11) may reflect the close relationship between the microtubular system and the cell membrane.…”

mentioning

confidence: 99%

A colchicine-sensitive uptake system in Morris hepatomas.

Tauber¹,

Reutter²

1980

Proc. Natl. Acad. Sci. U.S.A.

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' The interference of microtubular disruptors with the-uptake of amino acids and other low molecular weight substrates has been studied in Morris hepatomas, host liver, and regenerating liver. Colchicine inhibits amino acid transport (ct-aminoisobutyric acid, L-methionine, and L-leucine) in hepatomas by 59-98% whereas transport in host and regenerating liver is not impeded but increased. In hepatomas, treatment with colchicine also reduces the uptake of L-fcose, cytidine, urea, and carbonate. Vinblastine, but not lumicolchicine or cytochalasin B, is an effective inhibitor. The inhibition of uptake is not linked to a decrease of cellular ATP and UTP. The data suggest that the transport of low molecular weight substrates in hepatomas is related to microtubules or other colchicine-binding structures, e.g., of the plasma membrane. This colchicine-sensitive uptake system in hepatomas may be due to the malignant transformation of hepatocytes.

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“…It has been shown by a number of investigators that colchicine suppresses the functions of polymorphonuclear leukocytes (7,(19)(20)(21). Its effects on mononuclear leukocytes have not been studied.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of action of colchicine

Chang

1975

Arthritis & Rheumatism

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Colchicine suppresses the development of carrageenan‐induced edema in the rat with a minimum effective oral dose of 6.0 mg/kg. The slope of the dose‐response regression line for colchicine differs significantly from that of indomethacin and phenylbutazone. Based on the dosages required to achieve a 50% suppression of this inflammation, colchicine is 0.6 and 1.5 times as potent as indomethacin and phenylbutazone, respectively. In the reversed passive Arthus reaction in the rat, the suppressive activity of colchicine is at least 50 times that of indomethacin and 100 times that of phenylbutazone. The possible significance of these results with regard to the unique effectiveness of colchicine in the treatment of gout is discussed.

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The Dissociation by Colchicine of Phagocytosis from Increased Oxygen Consumption in Human Leukocytes*

Cited by 160 publications

References 33 publications

Mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis: inhibition by colchicine and cortisol but not by salicylate

Mobilization and extracellular release of granular enzymes from human leukocytes during phagocytosis: inhibition by colchicine and cortisol but not by salicylate

A colchicine-sensitive uptake system in Morris hepatomas.

Mechanism of action of colchicine

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