Bronchoconstriction in nonhuman primates: a species comparison

Abstract

Bronchoconstriction is a characteristic symptom of various chronic obstructive respiratory diseases such as chronic obstructive pulmonary disease and asthma. Precision-cut lung slices (PCLS) are a suitable ex vivo model to study physiological mechanisms of bronchoconstriction in different species. In the present study, we established an ex vivo model of bronchoconstriction in nonhuman primates (NHPs). PCLS prepared from common marmosets, cynomolgus macaques, rhesus macaques, and anubis baboons were stimulated with increasing concentrations of representative bronchoconstrictors: methacholine, histamine, serotonin, leukotriene D₄ (LTD₄), U46619, and endothelin-1. Alterations in the airway caliber were measured and compared with previously published data from rodents, guinea pigs, and humans. Methacholine induced maximal airway constriction, varying between 74 and 88% in all NHP species, whereas serotonin was ineffective. Histamine induced maximal bronchoconstriction of 77 to 90% in rhesus macaques, cynomolgus macaques, and baboons and a lesser constriction of 53% in marmosets. LTD₄ was ineffective in marmosets and rhesus macaques but induced a maximum constriction of 44 to 49% in cynomolgus macaques and baboons. U46619 and endothelin-1 caused airway constriction in all NHP species, with maximum constrictions of 65 to 91% and 70 to 81%, respectively. In conclusion, PCLS from NHPs represent a valuable ex vivo model for studying bronchoconstriction. All NHPs respond to mediators relevant to human airway disorders such as methacholine, histamine, U46619, and endothelin-1 and are insensitive to the rodent mast cell product serotonin. Only PCLS from cynomolgus macaques and baboons, however, responded also to leukotrienes, suggesting that among all compared species, these two NHPs resemble the human airway mechanisms best.

Evaluation of inflammatory and immune responses in long-term cultured human precision-cut lung slices

“…Previous work on this technology have shown that PCLS can easily be prepared in abundance just from a single human lung lobe and can be prepared from human as well as different laboratory animal species, including mice, rats, guinea pigs, sheep and monkeys. [1][2][3][4][5] Multiple studies have focused on assessing various characteristics of cultured PCLS, such as measurement of bronchoconstriction [6][7][8] and vascular responses 9,10 induced by various stimuli. In addition, PCLS have been used to evaluate allergy, 11 asthma, 6 toxicology, [12][13][14] and infectious disease responses.…”

Study on bronchoconstriction induced by histamine or serotonin in “Precision Cut Lung Slices” of the horse

“…Previous work has demonstrated the high sensitivity of guinea pigs' (EC50=217 nM) (Ressemeyer et al 2006) and marmosets' (EC50=425 nM) (Seehase et al 2011) small airways to histamine. Studies on the horse provided variable results.…”

Comparison Of Airway Responses In Sheep Of Different Age In Precision-cut Lung Slices (PCLS)

“…The microarchitecture of lung tissue, i.e. airways and vessels embedded in the parenchyma, remains intact and permit physiological measurements [23][24][25][26]. Even nerves remain functional and can be specifically activated [29].…”

“…PCLS can easily be prepared from different species and are already established for many species including rat, mouse, guinea pig, non-human primates and humans [14,17,[23][24][25][26]. PCLS represent a highly useful model to study bronchial and pulmonary vascular responses by videomicroscopy [23,27].…”