Histamine-Containing Cells from Bronchial Lavage of Macaque Monkeys. Time Course and Inhibition of Anaphylactic Histamine Release

Butchers, P.R.; Vardey, C.J.; Skidmore, I.F.; Wheeldon, Alan; Boutal, L E

doi:10.1159/000232513

Cited by 9 publications

(3 citation statements)

References 5 publications

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“…However, despite the similarity of this model with human allergic asthma we were disappointed to find that SCG given by aerosol or intravenously did not inhibit Ascaris-induced increases in total lung resistance (RL) or falls in dynamic lung compliance (Cdy,). This lack of inhibition is consistent with the demonstration that SCG was a poor inhibitor in vitro of histamine release by Ascaris antigen from histaminecontaining cells obtained by bronchialveolar lavage of rhesus and cynomolgus monkeys [16].…”

Section: Alternative Modes Of Action Of Sodium Cromoglycatesupporting

confidence: 89%

Alternative modes of action of sodium cromoglycate

Richards

Dixon

Jackson³

et al. 1986

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Alternative modes of action of sodium cromoglycateSodium cromoglycate (SCG) remains a unique drug in the management of asthma. Despite the intensive efforts of many pharmaceutical companies [1] to replace SCG with a more potent, more efficacious, orally active or longer acting agent, SCG is the only drug of its type which has been accepted into clinical practice since the demonstration of its prophylactic activity by ALTOUNYAN [2]. The attempts to develop new 'anti-allergic' drugs have been extensively reviewed by others in this journal and elsewhere [1,3].Despite the general acceptance that the primary mode of action of cromoglycate is to stabilize the mast cell membrane and thus prevent the release of bronchoactive or inflammatory mediators, two major anomalies have emerged which contradict this view. The first is the demonstration of activity with sodium cromoglycate in man in some forms of asthmatic bronchoconstriction in which mast cells or allergic mechanisms may not be involved. Secondly, many novel compounds, far more potent than SCG in mast cell-mediated animal models, have demonstrated little or no efficacy when tested in the clinic. These anomalies will be discussed later but it may be relevant to point out here that much of the initial pioneering, experimental work with SCG was carried out in man [2] and the animal models followed! In this paper two parallel lines of research are reviewed in which we attempted to demonstrate activity with SCG in animal models of immediate, airway hypersensitivity or we investigated the effects of SCG on vagally-mediated reflex bronchoconstriction.The passive cutaneous anaphylaxis (PCA) test in rats was one of the first in vivo animal models in which cromoglycate was shown to be effective [4] and has since been used extensively in screening this type of compound. Our early attempts to develop a clinically relevant test in the airways for SCG-like activity included studies with passive lung anaphylaxis (PLA) in the rat [5,6]. Rats were sensitized by the intravenous injection of high titre reaginic antiserum prepared in rats [7] and twenty-four hours later the rats were anaesthetized and SCG and other anti-anaphylactic compounds were given 1 minute before challenge with antigen. Bronchoconstriction was measured by a modification of the method of KONZETT and ROSSLER [8]. The IDs0 for SCG as an inhibitor of PLA was found to be 1.3 mg/kg compared with 1.0 mg/kg in the PCA test. Comparison of the activity of 13 novel anti-anaphylactic compounds in the PCA tests and PLA tests resulted in a highly significant correlation (p < 0.001) when the dose-ratios of compounds relative to SCG were compared in both tests [5].In parallel with the investigation of the effects ofcromoglycate on anaphylactic bronchoconstriction in the rat, in vivo we were able to look at the drug's effects on the release of the ~ediators of anaphylactic bronchoconstriction in vitro. We did this using the technique of cascade superfusion of isolated tissues [9]. Using suitable assay tissues and appropriate ant...

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Section: Alternative Modes Of Action Of Sodium Cromoglycatesupporting

confidence: 89%

Alternative modes of action of sodium cromoglycate

Richards

Dixon

Jackson³

et al. 1986

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“…DSCG is a weak inhibitor of the antigen-induced release of histamine from human lung fragments (EC50 >180 ¿rg/ml) [5], from monkey bronchial la vage cells (EC50 >900 fig/ml) [6], from fragments of guinea pig lung (EC50 >80 /rg/ml) [1], and from hu man basophils (EC50 >300 /rg/ml) [1], In all these sys tems, a-chymotrypsin fails to induce the release of histamine. In contrast, a-chymotrypsin releases hista mine from rat cells and tissues and in these systems DSCG is an effective inhibitor with characteristic properties.…”

Section: Discussionmentioning

confidence: 99%

“…[6], cells were lavaged from the bronchial lumen of an Ascaris-sensitive rhesus monkey. The procedure to investigate histamine release was as described above.…”

Section: Methodsmentioning

confidence: 99%

The Release of Histamine from Rat Mast Cells by Chymotrypsin

Nials¹,

Vardey²,

Skidmore³

1983

Int Arch Allergy Immunol

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The release of histamine from rat peritoneal mast cells induced by α-chymotrypsin and that induced by antigen have characteristics in common. The kinetics of histamine release initiated by the two agents are similar. Both α-chymotrypsin and antigen release histamine in the absence of extracellular calcium, phosphatidyl serine enhances the release, and disodium cromoglycate inhibits both reactions. In contrast, extracellular α-chymotrypsin does not induce histamine release from cells isolated from fragments of human lung, human basophils, histamine-containing cells lavaged from the bronchial lumen of the rhesus monkey, fragments of human lung and fragments of guinea pig lung.

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Orthopedic surgery

1983

Arthritis & Rheumatism

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Histamine-Containing Cells from Bronchial Lavage of Macaque Monkeys. Time Course and Inhibition of Anaphylactic Histamine Release

Cited by 9 publications

References 5 publications

Alternative modes of action of sodium cromoglycate

Alternative modes of action of sodium cromoglycate

The Release of Histamine from Rat Mast Cells by Chymotrypsin

Orthopedic surgery

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