Density heterogeneity of human lung mast cells

Abstract

Suspensions of enzymatically dispersed human lung parenchymal mast cells were fractionated according to density by flotation through discontinuous Percoll gradients and examined for their responsiveness to release stimulants and pharmacologic agonists. Mast cells localized to all six density fractions (I–VI) examined; densities varied from specific gravities of 1.053 gm/ml to 1.123 gm/ml. Most (67%) lung mast cells localized to fractions III and IV, corresponding to specific gravities of 1.077 to 1.088 gm/ml, respectively. Histamine content increased with density from 2.7 ± 0.3 pg per cell in fraction I to 4.8 ± 0.7 pg per cell in fraction VI (mean ± SEM; n = 19). Fraction III was least responsive to high concentrations of anti-IgE than to any other fractions and, along with fraction IV, the most responsive to ionophore A23187. All fractions released the arachidonate mediators prostaglandin D 2 and leukotriene C 4 in response to anti-IgE. In four of eight lungs tested, formyl methionine peptide (10 −6 to 10 −4 mol/L) weakly elicited histamine release (3% to 6%) in fractions I and II cells. Compound 48 80 (0.1 to 10 μg/ml; n = 3) failed to induce histamine release in any fractions. The cyclic adenosine monophosphate-active drugs, isoproterenol (10 −4 mol/L), dibutyryl cyclic adenosine monophosphate (3 mmol/L), and isobutylmethylxanthine (3 × 10 −4 mol/L) inhibited anti-IgE-induced histamine release from all fractions equivalently. Dimaprit (3 × 10 −5 mol/L) and cromolyn sodium (10 −5 − 3 × 10 −3 mol/L) failed to significantly inhibit any fraction. Nordihydroguaiarectic acid (3 × 10 −5 mol/L; n = 6) markedly inhibited histamine release from fractions III to VI but had no significant effects on fractions I and II mast cells. We conclude that mast cells from human lung are morphologically heterogeneous with respect to density. These density subsets differ functionally in their responsiveness to secretagogues and to nordihydroguaiaretic acid.