Late pulmonary responses induced by Ascaris allergen in conscious squirrel monkeys

Abstract

This study presents an antigen-dependent model of biphasic pulmonary changes to Ascaris suum in conscious squirrel monkeys. Animals with strong positive skin reactivity towards A. suum were trained to sit quietly in chairs and to breathe through face masks. Dynamic compliance (Cdyn) and pulmonary resistance (RL) were measured in these conscious animals before and for a period of 11 h after administration of an aerosol of Ascaris or ragweed antigen. The aerosol of Ascaris antigen induced reproducible increases (42%) in RL (P less than 0.001) and decreases (17%) in Cdyn (P less than 0.01) that peaked respectively 5 and 35 min after antigen challenge and lasted 60-90 min. After recovery, a second bronchoconstriction began between 2 and 8 h and peaked between 4 and 10 h after antigen challenge. Decreases in Cdyn (41%) were significantly greater (P less than 0.003) whereas mean increases in RL (44%) were similar during the late phase as compared with the first phase. The mean Cdyn decreases lasted a minimum of 2 h, whereas RL increases lasted less than 60 min. The time course of the responses varied from animal to animal but changes in individual animals were reproducible over a period of 6 mo. No significant correlation was observed between the cutaneous and the pulmonary responses to Ascaris and the late response was not reversed by aerosol administration of salbutamol (1.0 mg/ml). As a negative control animals were exposed to an aerosol of ragweed extract after which no immediate or late pulmonary response were observed. The results suggest that this primate model may be useful to study the pathophysiology of asthma in humans.

Animal models of occupational asthma

“…Results of challenge with Ascaris antigen indicated that pulmonary changes occurred in the absence of any significant variations in f or VT [58]. Late responses occurred in four of nine animals which demonstrated early reactions.…”

“…Naturally sensitized, conscious squirrel monkeys have demonstrated immediate and late-phase responses upon aerosol challenge with Ascaris antigen [58]. Aerosol challenge was given through a face mask for a 6 min period.…”

“…The model has many similarities to human asthma, in that some populations have persistent allergen-triggered asthma, others have spontaneous subsidence of asthma but remain skin test positive, and others have positive skin tests with no asthma [58]. Attempts to develop a sensitive colony by deliberate parasitic infection of primates using A. suum ova, resulted in cutaneous and respiratory reactivity, however the latter typically lasted for less than 1 yr.…”

An etiological role for aeroallergens and eosinophils in experimental esophagitis

“…The TRFK-5 hybridoma was purchased from American Type Culture Collection (Rockville, Maryland, USA), grown in ascites fluid, and the antibody was partially purified by ammonium sulfate precipitation. In some experiments, anesthetized mice were exposed to nine doses (25 µl) of intranasal Ascaris pseudocoelomic fluid (APF; a kind gift of Joseph Urban, US Department of Agriculture, Bellville, Maryland, USA, and Fred Finkelman, University of Cincinnati, Cincinnati, Ohio, USA) (23)(24)(25)(26) on alternate days and analyzed 18 hours after the last allergen challenge. In other experiments, mice were sensitized by intraperitoneal injection of 50 µg of ovalbumin (OVA) and 1 mg alum in 0.9% sterile saline on two occasions separated by 14 days.…”

Eotaxin and Nitric Oxide Production as Markers of Inflammation in Allergic Cynomolgus Monkeys

“…Pulmonary hypersensitivity to exogenous antigen has been studied in the squirrel monkey ( Saimiri sciureus [1]), rhesus monkey ( Macaca mulatta [2]), Japanese monkey ( Macaca fuscata [3]) and cynomolgus monkey ( Macaca fascicularis [4]). The most common antigen used is an extract of Ascaris suum because a high percentage of these species of nonhuman primates show a natural hypersensitivity to this antigen.…”