Summary The NB1 glycoprotein (CD177, HNA‐2a antigen) is exclusively expressed on human neutrophils. As the clinical significance of CD177 expression is unknown, we investigated its expression in healthy individuals before and after stimulation with granulocyte colony‐stimulating factor (G‐CSF), in patients with rheumatoid arthritis, viral hepatitis, severe bacterial infections and polycythaemia vera. Expression was quantitatively determined by flow cytometry and by real time polymerase chain reaction. Only G‐CSF‐stimulated individuals and patients with severe bacterial infections and polycythaemia showed a significantly (P < 0·001) increased CD177 expression compared with healthy individuals, indicating that neutrophil CD177 expression can increase significantly in certain clinical conditions.

These findings show a significantly increased CD 177 expression in neutrophils from newborns compared to adults, which suggests the existence of additional factors being able to stimulate CD 177 expression.

Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high molecular weight kininogen (HK) in plasma of CAP patients and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of CAP patients (n=139) as compared to age-matched donors (n=58). No simultaneous decrease in FXII levels, indicating its consumption, was observed. Stratification by sex revealed augmented FXII levels in plasma of CAP women as compared to sex-matched donors yet no apparent differences in men. This sex-specific effect was, however, attributable to lower FXII levels in female donors relative to men donors. Plasma estradiol levels mirrored those for FXII. Levels of HK/albumin ratio were decreased in CAP plasma as compared to donors, however, after stratification by sex, this difference was only observed in women and was related to higher HK/albumin values in female donors as opposed to male donors. Finally, strong negative correlation between plasma levels of HK/albumin ratio and CAP severity, as assessed by CRB65 score, in males and females was observed. Our study identifies sex-dependent differences in plasma levels of the contact phase proteins in elderly subjects that may contribute to specific clinical outcomes in CAP between men and women.

Background: Sex-dependent differences in immunity and coagulation play an active role in 28 the outcome of community-acquired pneumonia (CAP). Factor XII acts at the crossroads 29 between inflammation and coagulation thus representing a point of convergence in host 30 defense against infection. Here, we evaluated FXII/FXIIa levels in plasma of CAP patients 31 and correlated them to clinical disease severity.Methods and Results: FXII was activated in CAP plasma as evident by the presence of 33 FXIIa-C1-esterase inhibitor (C1INH) complexes. The levels of FXIIa-C1INH complexes 34 were elevated in plasma of CAP patients (n=140) as compared to age- and sex-matched 35 healthy controls (n=58; p<0.001). No simultaneous decrease in FXII levels, indicating its 36 consumption, was observed. Stratification by sex revealed augmented levels of FXII in 37 plasma of CAP women as compared to healthy females (p=0.008) yet no apparent differences 38 in men (p=0.619). This sex-specific difference was, however, attributable to the lower levels 39 of FXII in healthy females relative to healthy men (p=0.011). Upon contact with CAP plasma, 40 isolated blood neutrophils released FXII and female blood neutrophils were able to re-induce 41 FXII mRNA synthesis (p=0.031). Despite this sex-specific effect, exposure of female blood 42 neutrophils to estradiol did not induce FXII mRNA expression. Finally, although we observed 43 accumulation of FXIIa-C1INH complexes in plasma of severe CAP patients, the relationship 44 between the levels of FXIIa-C1INH complexes and CAP severity, as assessed by CRB65 45 score, did not reach statistical significance (p=0.057). 46Conclusions: Our study identifies age- and sex-dependent differences in FXII expression that 47 may contribute to specific clinical outcomes in CAP in different patient subgroups.

Mice that underwent a unilateral pneumonectomy (PNX) show complete restoration of pulmonary function through a rapid and complete compensatory growth of the remaining lung. Currently there is still little known about the nature, initiation and modulation of such growth. Microarray studies showed an upregulated expression of the immediate early gene Egr1 and the matricellular protein Tnc after PNX. In this study we assess the role of Egr1 and Tnc in early stages of compensatory lung growth. Stereology analysis of tissue sections showed that lungs of Egr−/− mice have the same surface area but less alveoli and a larger lung volume compared to wild type mice. During compensatory lung growth the loss of Egr1 seems to lead to a delayed regeneration of alveolar surface area whereas lung volume increases faster. Stereological analysis of Tnc−/− mice showed that these mice also have a larger lung volume compared to wild type mice. After PNX regeneration of alveolar number and lung volume is impaired. The results indicate that Egr1 and Tnc seem to have an influential role in the initial phases of compensatory lung growth. Additional experiments will be done to clarify how these genes are regulated after PNX. German research foundation.