Figure 6.

Strategies aimed at diminution of bronchus-associated lymphoid tissues (BALTs) biology prevent and reverse pulmonary hypertension (PH). (A) Preventing lung cell apoptosis (and presumably self-antigen burden) by salubrinal (Sal), an unfolded protein response modulator, prevents and reverses pulmonary vascular remodeling and PH in a manner associated with decreased BALT size and number. (B) Pharmacologic VEGFR3 antagonism prevents and reverses monocrotaline (MCT)-PH and is associated with decreased macrophage influx, decreased blood and lymphatic vascularization, and smaller BALT size and numbers. (C) CCR7 controls migration of lung CCR7⁺ dendritic cells (DC) and CCR7⁺ T cells into BALT; pharmacologic CCR7 antagonism worsens MCT-PH and is associated with larger BALT size and numbers. (D) Lymphotoxin β receptor (LTBR) control animals BALT formation and maintenance; pharmacologic LTBR antagonism prevents and reverses MCT-PH and is associated with decreased blood and lymphatic vascularization, and smaller BALT size and numbers. In A–D, pressure measurement, BALT counts, and representative lung section images were taken from n = 6 animals per group, with two to three sections per rat from three independent experiments. All images, original magnification: ×100. *P less than 0.05 compared with control, Student t test. (E) Representative laser capture microdissection of BALT from rat lung section. Black arrows show the microdissected BALT region. The table lists the mRNAs isolated from the rat groups and their respective mean fold changes in expression relative to the control lung BALT. n = 2–3 BALT per section, 3–5 sections per rat, n = 6 animals per group. For each fold change equal to or greater than ± 1.2 fold, P less than 0.05 compared with control using Student t test. CTL = control; Maz = Maz51 VEGFR3 inhibitor.