Acyloxyacyl hydrolase promotes pulmonary defense by preventing alveolar macrophage tolerance.

Although alveolar macrophages (AMs) play important roles in preventing and eliminating pulmonary infections, little is known about their regulation in healthy animals. Since exposure to LPS often renders cells hyporesponsive to subsequent LPS exposures ("tolerant"), we tested the hypothesis that LPS produced in the intestine reaches the lungs and stimulates AMs, rendering them tolerant. We found that resting AMs were more likely to be tolerant in mice lacking acyloxyacyl hydrolase (AOAH), the host lipase that degrades and inactivates LPS; isolated Aoah-/- AMs were less responsive to LPS stimulation and less phagocytic than were Aoah+/+ AMs. Upon innate stimulation in the airways, Aoah-/- mice had reduced epithelium- and macrophage-derived chemokine/cytokine production. Aoah-/- mice also developed greater and more prolonged loss of body weight and higher bacterial burdens after pulmonary challenge with Pseudomonas aeruginosa than did wildtype mice. We also found that bloodborne or intrarectally-administered LPS desensitized ("tolerized") AMs while antimicrobial drug treatment that reduced intestinal commensal Gram-negative bacterial abundance largely restored the innate responsiveness of Aoah-/- AMs. Confirming the role of LPS stimulation, the absence of TLR4 prevented Aoah-/- AM tolerance. We conclude that commensal LPSs may stimulate and desensitize (tolerize) alveolar macrophages in a TLR4-dependent manner and compromise pulmonary immunity. By inactivating LPS in the intestine, AOAH promotes antibacterial host defenses in the lung.

[Relationship between Chinese medicine pattern with blood levels of sex hormone, lipid and glucose in climacteric women patients with hypertension].

OBJECTIVE: To find the objective indices for traditional Chinese medicine (TCM) pattern identification in women patients with climacteric hypertension (CH) by exploring the relationship between TCM pattern with blood levels of sex hormone, lipid and glucose. METHODS: TCM syndrome differentiation was made in 75 women CH patients, 43 as yin-deficiency with inner dryness pattern (YDD) and 32 as non-YDD, and correlation analyses were conducted on TCM patterns and blood levels of estradiol (E2), lipids and glucose. RESULTS: Besides the level of E2 in YDD was lower than that in non-YDD [(112.26 -/+ 66.81) pmol/L vs (146.69 +/- 83.59) pmol/L, P < 0.05), no difference between the two patterns was found in the other indices measured (P > 0.05). Further subunit analysis showed that in patients with CH grade 1, blood levels of total cholesterol (TC), high density lipoprotein (HDL) and apoprotein A-I (ApoA-I) were higher in the 13 patients of YDD than those in the 9 of non-TDD (P < 0.05); in patients with CH grade 2, levels of E2, progesterone (T), HDL and ApoA-I were lower but level of follicle stimulating hormone (FSH) was higher in the 20 YDD than those in the 10 non-YDD (all P < 0.05); while in patients with CH grade, no statistically significant difference was shown between 3 patients of 10 with YDD and 13 with non-YDD in all the indices measured (P > 0.05). CONCLUSION: Blood level of E2 shows different characteristics between CH patients of YDD and non-YDD patterns, suggesting that it may provide some help to syndrome micro-differentiation, and taking it as an objective index for syndrome typing of climacteric hypertension in female is considerable.